Structural Patterns Enhancing the Antibacterial Activity of Metallacarborane-Based Antibiotics

Abstract

Healthcare systems heavily rely on antibiotics to treat bacterial infections, but the widespread presence of multidrug-resistant bacteria puts this strategy in danger. Novel drugs capable of overcoming current resistances are needed if our ability to treat bacterial infections is to be maintained. Boron clusters offer a valuable possibility to create a new class of antibiotics and expand the chemical space of antibiotics beyond conventional carbon-based molecules. In this work, we identified two promising structural patterns providing cobalta bis(dicarbollide)(COSAN)-based compounds with potent and selective activity toward <i>Staphylococcus aureus</i> (including clinical strains): introduction of the α-amino acid amide and addition of iodine directly to the metallacarborane cage. Furthermore, we found that proper hydrophilic-lipophilic balance is crucial for the selective activity of the tested compounds toward <i>S. aureus</i> over mammalian cells. The patterns proposed in this paper can be useful in the development of metallacarborane-based antibiotics with potent antibacterial properties and low cytotoxicity.